scholarly journals AMIGO, a transmembrane protein implicated in axon tract development, defines a novel protein family with leucine-rich repeats

2003 ◽  
Vol 160 (6) ◽  
pp. 963-973 ◽  
Author(s):  
Juha Kuja-Panula ◽  
Marjaana Kiiltomäki ◽  
Takashi Yamashiro ◽  
Ari Rouhiainen ◽  
Heikki Rauvala
Keyword(s):  
Hippocampal Neurons ◽  
Transmembrane Domain ◽  
Signal Sequence ◽  
Transmembrane Protein ◽  
Protein Family ◽  
Type I ◽  
Fiber Tracts ◽  
Neuronal Tissues ◽  
Immunoglobulin Domain ◽  
Leucine Rich Repeats

Ordered differential display identified a novel sequence induced in neurons by the neurite-promoting protein amphoterin. We named this gene amphoterin-induced gene and ORF (AMIGO), and also cloned two other novel genes homologous to AMIGO (AMIGO2 and AMIGO3). Together, these three AMIGOs form a novel family of genes coding for type I transmembrane proteins which contain a signal sequence for secretion and a transmembrane domain. The deduced extracellular parts of the AMIGOs contain six leucine-rich repeats (LRRs) flanked by cysteine-rich LRR NH2- and COOH-terminal domains and by one immunoglobulin domain close to the transmembrane region. A substrate-bound form of the recombinant AMIGO ectodomain promoted prominent neurite extension in hippocampal neurons, and in solution, the same AMIGO ectodomain inhibited fasciculation of neurites. A homophilic and heterophilic binding mechanism is shown between the members of the AMIGO family. Our results suggest that the members of the AMIGO protein family are novel cell adhesion molecules among which AMIGO is specifically expressed on fiber tracts of neuronal tissues and participates in their formation.

scholarly journals Canine Influenza Virus is Mildly Restricted by Canine Tetherin Protein

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 565
Author(s):  
Yun Zheng ◽  
Xiangqi Hao ◽  
Qingxu Zheng ◽  
Xi Lin ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Cellular Damage ◽  
Interferon Response ◽  
Type I ◽  
Canine Influenza Virus ◽  
Immune Factor ◽  
Canine Influenza ◽  
The Impact

Tetherin (BST2/CD317/HM1.24) has emerged as a key host-cell ·defence molecule that acts by inhibiting the release and spread of diverse enveloped virions from infected cells. We analysed the biological features of canine tetherin and found it to be an unstable hydrophilic type I transmembrane protein with one transmembrane domain, no signal peptide, and multiple glycosylation and phosphorylation sites. Furthermore, the tissue expression profile of canine tetherin revealed that it was particularly abundant in immune organs. The canine tetherin gene contains an interferon response element sequence that can be regulated and expressed by canine IFN-α. A CCK-8 assay showed that canine tetherin was effective in helping mitigate cellular damage caused by canine influenza virus (CIV) infection. Additionally, we found that the overexpression of canine tetherin inhibited replication of the CIV and that interference with the canine tetherin gene enhanced CIV replication in cells. The impact of canine tetherin on CIV replication was mild. However, these results elucidate the role of the innate immune factor, canine tetherin, during CIV infection for the first time.

scholarly journals Atypical Fusion Peptide of Nelson Bay Virus Fusion-Associated Small Transmembrane Protein

2005 ◽  
Vol 79 (3) ◽  
pp. 1853-1860 ◽  
Author(s):  
LiTing T. Cheng ◽  
Richard K. Plemper ◽  
Richard W. Compans
Keyword(s):  
Transmembrane Domain ◽  
Mutational Analysis ◽  
Transmembrane Protein ◽  
Syncytium Formation ◽  
Surface Expression ◽  
Fusion Peptide ◽  
Cell Surface Expression ◽  
Type I ◽  
Fusion Activity ◽  
Hydrophobic Domain

ABSTRACT A 10-kDa nonstructural transmembrane protein (p10) encoded by a reovirus, Nelson Bay virus, has been shown to induce syncytium formation (34). Sequence analysis and structural studies identified p10 as a type I membrane protein with a central transmembrane domain, a cytoplasmic basic region, and an N-terminal hydrophobic domain (HD) that was hypothesized to function as a fusion peptide. We performed mutational analysis on this slightly hydrophobic motif to identify possible structural requirements for fusion activity. Bulky aliphatic residues were found to be essential for optimal fusion, and an aromatic or highly hydrophobic side chain was found to be required at position 12. The requirement for hydrophilic residues within the HD was also examined: substitution of 10-Ser or 14-Ser with hydrophobic residues was found to reduce cell surface expression of p10 and delayed the onset of syncytium formation. Nonconservative substitutions of charged residues in the HD did not have an effect on fusion activity. Taken together, our results suggest that the HD is involved in both syncytium formation and in determining p10 transport and surface expression.

scholarly journals Sec12p requires Rer1p for sorting to coatomer (COPI)-coated vesicles and retrieval to the ER

1997 ◽  
Vol 110 (8) ◽  
pp. 991-1003 ◽  
Author(s):  
J. Boehm ◽  
F. Letourneur ◽  
W. Ballensiefen ◽  
D. Ossipov ◽  
C. Demolliere ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Transmembrane Proteins ◽  
Type I ◽  
Dependent Manner ◽  
Type Ii ◽  
Retrieval Process ◽  
Hybrid Proteins ◽  
Er Retention ◽  
Golgi Compartment

In Saccharomyces cerevisiae cells lacking the Rer1 protein (Rer1p), the type II transmembrane protein Sec12p fails to be retained in the ER. The transmembrane domain of Sec12p is sufficient to confer Rer1p-dependent ER retention to other membrane proteins. In rer1 mutants a large part of the Sec12-derived proteins can escape to the late Golgi. In contrast, rer3 mutants accumulate Sec12-derived hybrid proteins carrying early Golgi modifications. We found that rer3 mutants harbour unique alleles of the alpha-COP-encoding RET1 gene. ret1 mutants, along with other coatomer mutants, fail to retrieve KKXX-tagged type I transmembrane proteins from the Golgi back to the ER. Surprisingly rer3-11(=ret1-12) mutants do not affect this kind of ER recycling. Pulse-chase experiments using these mutants show that alpha-COP and Rer1p function together in a very early Golgi compartment to initiate the recycling of Sec12p-derived hybrid proteins. Rer1p protein may be directly involved in the retrieval process since it also recycles between the early Golgi and ER in a coatomer (COPI)-dependent manner. Rer1p may act as an adapter coupling the recycling of non-KKXX transmembrane proteins like Sec12p to the coatomer (COPI)-mediated backward traffic.

scholarly journals Steady-State Plasma Membrane Expression of Human Cytomegalovirus gB Is Determined by the Phosphorylation State of Ser900

1998 ◽  
Vol 72 (8) ◽  
pp. 6657-6664 ◽  
Author(s):  
Kenneth N. Fish ◽  
Cecilia Soderberg-Naucler ◽  
Jay A. Nelson
Keyword(s):  
Plasma Membrane ◽  
Steady State ◽  
Amino Acid ◽  
Human Cytomegalovirus ◽  
Transmembrane Domain ◽  
Signal Sequence ◽  
Amino Acid Type ◽  
Type I ◽  
Intracellular Compartments ◽  
U373 Cells

ABSTRACT Human cytomegalovirus (HCMV) infection of an astrocytoma cell line (U373) or human fibroblast (HF) cells results in a differential cell distribution of the major envelope glycoprotein gB (UL55). This 906-amino-acid type I glycoprotein contains an extracellular domain with a signal sequence, a transmembrane domain, and a 135-amino-acid cytoplasmic tail with a consensus casein kinase II (CKII) site located at Ser900. Since phosphorylation of proteins in the secretory pathway is an important determinant of intracellular trafficking, the state of gB phosphorylation in U373 and HF cells was examined. Analysis of cells expressing wild-type gB and gB with site-specific mutations indicated that the glycoprotein was equally phosphorylated at a single site, Ser900, in both U373 and HF cells. To assess the effect of charge on gB surface expression in U373 cells, Ser900 was replaced with an aspartate (Asp) or alanine (Ala) residue to mimic the phosphorylated and nonphosphorylated states, respectively. Expression of the Asp but not the Ala gB mutation resulted in an increase in the steady-state expression of gB at the plasma membrane (PM) in U373 cells. In addition, treatment of U373 cells with the phosphatase inhibitor tautomycin resulted in the accumulation of gB at the PM. Interestingly, the addition of a charge at Ser900 trapped gB in a low-level cycling pathway at the PM, preventing trafficking of the protein to thetrans-Golgi network or other intracellular compartments. Therefore, these results suggest that a tautomycin-sensitive phosphatase regulates cell-specific PM retrieval of gB to intracellular compartments.

scholarly journals A role for BiP as an adjustor for the endoplasmic reticulum stress-sensing protein Ire1

2004 ◽  
Vol 167 (3) ◽  
pp. 445-456 ◽  
Author(s):  
Yukio Kimata ◽  
Daisuke Oikawa ◽  
Yusuke Shimizu ◽  
Yuki Ishiwata-Kimata ◽  
Kenji Kohno
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Binding Site ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Sensory System ◽  
Type I ◽  
Stress Signal ◽  
Stress Sensing ◽  
The Unfolded Protein Response

In the unfolded protein response, the type I transmembrane protein Ire1 transmits an endoplasmic reticulum (ER) stress signal to the cytoplasm. We previously reported that under nonstressed conditions, the ER chaperone BiP binds and represses Ire1. It is still unclear how this event contributes to the overall regulation of Ire1. The present Ire1 mutation study shows that the luminal domain possesses two subregions that seem indispensable for activity. The BiP-binding site was assigned not to these subregions, but to a region neighboring the transmembrane domain. Phenotypic comparison of several Ire1 mutants carrying deletions in the indispensable subregions suggests these subregions are responsible for multiple events that are prerequisites for activation of the overall Ire1 proteins. Unexpectedly, deletion of the BiP-binding site rendered Ire1 unaltered in ER stress inducibility, but hypersensitive to ethanol and high temperature. We conclude that in the ER stress-sensory system BiP is not the principal determinant of Ire1 activity, but an adjustor for sensitivity to various stresses.

scholarly journals Genetic Analysis of Determinants for Spike Glycoprotein Assembly into Murine Coronavirus Virions: Distinct Roles for Charge-Rich and Cysteine-Rich Regions of the Endodomain

2004 ◽  
Vol 78 (18) ◽  
pp. 9904-9917 ◽  
Author(s):  
Rong Ye ◽  
Cynthia Montalto-Morrison ◽  
Paul S. Masters
Keyword(s):  
Transmembrane Domain ◽  
Mutational Analysis ◽  
Hepatitis Virus ◽  
Transmembrane Protein ◽  
Terminal Segment ◽  
Type I ◽  
Viral Fusion ◽  
S Protein ◽  
Infected Cells ◽  
Carboxy Terminal

ABSTRACT The coronavirus spike protein (S) forms the distinctive virion surface structures that are characteristic of this viral family, appearing in negatively stained electron microscopy as stems capped with spherical bulbs. These structures are essential for the initiation of infection through attachment of the virus to cellular receptors followed by fusion to host cell membranes. The S protein can also mediate the formation of syncytia in infected cells. The S protein is a type I transmembrane protein that is very large compared to other viral fusion proteins, and all except a short carboxy-terminal segment of the S molecule constitutes the ectodomain. For the prototype coronavirus mouse hepatitis virus (MHV), it has previously been established that S protein assembly into virions is specified by the carboxy-terminal segment, which comprises the transmembrane domain and the endodomain. We have genetically dissected these domains in the MHV S protein to localize the determinants of S incorporation into virions. Our results establish that assembly competence maps to the endodomain of S, which was shown to be sufficient to target a heterologous integral membrane protein for incorporation into MHV virions. In particular, mutational analysis indicated a major role for the charge-rich carboxy-terminal region of the endodomain. Additionally, we found that the adjacent cysteine-rich region of the endodomain is critical for fusion of infected cells, confirming results previously obtained with S protein expression systems.

scholarly journals Signal-mediated retrieval of a membrane protein from the Golgi to the ER in yeast.

1994 ◽  
Vol 127 (3) ◽  
pp. 653-665 ◽  
Author(s):  
E C Gaynor ◽  
S te Heesen ◽  
T R Graham ◽  
M Aebi ◽  
S D Emr
Keyword(s):  
Amino Acid ◽  
Fusion Protein ◽  
Mammalian Cells ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Minor Role ◽  
Type I ◽  
Dependent Manner ◽  
Coding Sequence ◽  
Golgi Compartment

The Saccharomyces cerevisiae Wbp1 protein is an endoplasmic reticulum (ER), type I transmembrane protein which contains a cytoplasmic dilysine (KKXX) motif. This motif has previously been shown to direct Golgi-to-ER retrieval of type I membrane proteins in mammalian cells (Jackson, M. R., T. Nilsson, and P. A. Peterson. 1993. J. Cell Biol. 121: 317-333). To analyze the role of this motif in yeast, we constructed a SUC2-WBP1 chimera consisting of the coding sequence for the normally secreted glycoprotein invertase fused to the coding sequence of the COOH terminus (including the transmembrane domain and 16-amino acid cytoplasmic tail) of Wbplp. Carbohydrate analysis of the invertase-Wbp1 fusion protein using mannose linkage-specific antiserum demonstrated that the fusion protein was efficiently modified by the early Golgi initial alpha 1,6 mannosyltransferase (Och1p). Subcellular fractionation revealed that > 90% of the alpha 1,6 mannose-modified fusion protein colocalized with the ER (Wbp1p) and not with the Golgi Och1p-containing compartment or other membrane fractions. Amino acid changes within the dily sine motif (KK-->QK, KQ, or QQ) did not change the kinetics of initial alpha 1,6 mannose modification of the fusion protein but did dramatically increase the rate of modification by more distal Golgi (elongating alpha 1,6 and alpha 1,3) mannosyltransferases. These mutant fusion proteins were then delivered directly from a late Golgi compartment to the vacuole, where they were proteolytically cleaved in a PEP4-dependent manner. While amino acids surrounding the dilysine motif played only a minor role in retention ability, mutations that altered the position of the lysines relative to the COOH terminus of the fusion protein also yielded a dramatic defect in ER retention. Collectively, our results indicate that the KKXX motif does not simply retain proteins in the ER but rather directs their rapid retrieval from a novel, Och1p-containing early Golgi compartment. Similar to observations in mammalian cells, it is the presence of two lysine residues at the appropriate COOH-terminal position which represents the most important features of this sorting determinant.

A 23bp Insertion in the Endothelial Protein C Receptor (EPCR) Gene Impairs EPCR Function

2001 ◽  
Vol 86 (10) ◽  
pp. 945-948 ◽  
Author(s):  
Giuliana Merati ◽  
Patricia Liaw ◽  
Paolo Bucciarelli ◽  
Natalia Oganesyan ◽  
Dongfeng Qu ◽  
...  
Keyword(s):  
Protein C ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Activated Protein C ◽  
Type I ◽  
Endothelial Protein C Receptor ◽  
Vein Thrombosis ◽  
Expression Studies ◽  
Deep Vein ◽  
Activation Capacity

SummaryEPCR is a type I transmembrane protein, highly expressed on the endothelium of large vessels, that binds protein C and augments its activation. In this study, a 23bp insertion in the EPCR gene was found in 4/198 survivors of myocardial infarction and 3/194 patients with deep vein thrombosis. The EPCR gene with the insertion predicts a protein that lacks part of the extracellular domain, the transmembrane domain and the cytoplasmic tail. Expression studies showed that the truncated protein is not localized on the cell surface, cannot be secreted in the culture medium, and does not bind activated protein C. Since protein C activation depends on the concentration of EPCR, patients with the EPCR insertion could have a diminished protein C activation capacity. Further clinical studies of adequate samples size are necessary to establish whether or not the EPCR insertion predisposes to the development of thrombotic events.

scholarly journals Yaba-like disease virus protein Y144R, a member of the complement control protein family, is present on enveloped virions that are associated with virus-induced actin tails

2004 ◽  
Vol 85 (5) ◽  
pp. 1279-1290 ◽  
Author(s):  
Mansun Law ◽  
Michael Hollinshead ◽  
Han-Joo Lee ◽  
Geoffrey L. Smith
Keyword(s):  
Disease Virus ◽  
Transmembrane Protein ◽  
Protein Family ◽  
Membrane Topology ◽  
Virus Protein ◽  
Type I ◽  
Complement Control Protein ◽  
Enveloped Virus ◽  
Infected Cells ◽  
Control Protein

Yaba-like disease virus (YLDV) is a yatapoxvirus, a group of slow-growing poxviruses from primates. Analysis of the growth cycle of YLDV in tissue culture showed that maximum virus titres were reached 3 days post-infection and at this time only 3·3 % of infectious progeny was extracellular. The intracellular and extracellular virions have different buoyant densities and are separable on CsCl density gradients. They are also distinguishable by electron microscopy with the extracellular virions having an additional lipid envelope. In YLDV-infected cells, thick actin bundles with virions at their tips were seen protruding from the cell surface, despite the fact that YLDV lacks a protein comparable to Vaccinia virus A36R, which is required for VV-induced actin tail formation. In addition to these observations, the YLDV gene Y144R was characterized. This gene is predicted to encode a transmembrane protein containing three short consensus repeat (SCR) motifs common to members of the complement control protein family. Antibody generated against recombinant Y144R recognized products of 36, 41 and 48–55 kDa in YLDV-infected cells and purified extracellular enveloped virus (EEV) but not intracellular mature virus (IMV). Y144R protein is a glycoprotein with type I membrane topology that is synthesized early and late during infection. By immunoblot, indirect immunofluorescence and immuno-cryoelectron microscopy the Y144R protein was detected on the intracellular enveloped virus (IEV), cell-associated enveloped virus (CEV) and EEV. This represents the first study of a YLDV IEV, CEV and EEV protein at the molecular level.

scholarly journals MEGF9: a novel transmembrane protein with a strong and developmentally regulated expression in the nervous system

2006 ◽  
Vol 401 (2) ◽  
pp. 447-457 ◽  
Author(s):  
Ulrike Brandt-Bohne ◽  
Douglas R. Keene ◽  
Fletcher A. White ◽  
Manuel Koch
Keyword(s):  
Nervous System ◽  
Glial Cells ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Developmentally Regulated ◽  
Putative Receptor ◽  
Glycosylation Sites ◽  
Signalling Molecule ◽  
Neuronal Tissues ◽  
Epidermal Growth

MEGF9 [multiple EGF (epidermal growth factor)-like-domains 9], a novel transmembrane protein with multiple EGF-like repeats, is predominantly expressed in the developing and adult CNS (central nervous system) and PNS (peripheral nervous system). The domain structure of MEGF9 consists of an N-terminal region with several potential O-glycosylation sites followed by five EGF-like domains, which are highly homologous with the short arms of laminins. Following one single pass transmembrane domain, a highly conserved short intracellular domain with potential phosphorylation sites is present. The protein was recombinantly expressed and characterized as a tissue component. To study the expression pattern further, immunohistochemistry was performed and staining was detected in Purkinje cells of the cerebellum and in glial cells of the PNS. Additional expression was observed in the epidermal layer of skin, papillae of the tongue and the epithelium of the gastrointestinal tract. By immunoelectron microscopy, MEGF9 was detected in glial cells of the sciatic nerve facing the basement membrane. MEGF9 represents a novel putative receptor, expressed in neuronal and non-neuronal tissues, that is regulated during development and could function as a guidance or signalling molecule.

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